Ageing

Question 1

What is the hayflick phenomenon?

Answer 1

Hayflick phenomenon of cellular ageing:

In tissue cultures of normal diploid cells, cells eventually cease to replicate unless transformed.
Mechanism unknown - but telomere shortening is involved.

Question 2

Four cellular mechanisms of ageing:

what are mechanisms at a cellular level that contribute to ageing at that level?

Answer 2

Four cellular mechanisms of ageing:

1. DNA mutation accumulation
2. Telomerase activity / telomere shortening (decreased ability for cellular replication)
3. Mitochondrial damage (oxidative damage)
   [metabolically active tissues]
4. Altered protein, waste accumulation
   [low turnover tissues]

Question 3

Molecular mechanisms of ageing:

Answer 3

.

Question 4

In Ageing, at what rate does the effectiveness of most physiological functions (nerve conduction velocity, cardiac index, GFR, maximal breathing capacity) decline?
[for the purposes of the exam]

Answer 4

The effectiveness of several physiological functions (nerve conduction velocity, cardiac index, GFR, maximal breathing capacity) decline at different rates, but on average:

Approximately 1% per year

Question 5

CV changes with ageing - at rest or with stress?

Answer 5

Resting HR and resting CO essentially unchanged.

Ability to respond to stress decreases:

• increased myocardial stiffness
• heart weight increases
• decreased max HR (220-age in years)
• decline in reserve function
• drop in peak CO

Question 6

Cardiovascular responsiveness to beta agonists - how does it change with age?

Answer 6

Decreased responsiveness to beta agonists with age - this is due to decreased receptor concentrations

Note also:

• Decreased vagal influence (less sensitive to atropine - but paradoxically more sensitive to carotid sinus massage).
• SA node fibrosis.
• Loss of cells in conducting system.

Question 7

Neurological examination abnormalities that occur with ageing:

eyes
gait
reflexes

peripheral nerves?

Answer 7

1. limitation of upward gaze
2. saccadic pursuit (cf. smooth eye movements)
3. paratonia (gegenhalten)
4. slow / stiff gait
5. Myerson’s sign (persistent glabellar blink response - NOT USEFUL IN ASSESSMENT OF PD IN ELDERLY) also present with normal ageing
6. balance disturbances, slow muscle responses
7. frontal release reflexes (snout, suck, root, grasp, palmo-mental)

— in the PNS —
can see reduced nerve conduction velocity (around 1% per yr) and loss of distal vibration sense and ankle reflexes IN NORMAL ELDERLY

Question 8

Why is it less common to see a WCC rise in the elderly with infection?

Answer 8

Normal production of granulocytes when unstressed.

Decreased response to GCSF –> decrease reserve when stressed

Question 9

Drug volume-of-distribution in the elderly:

Answer 9

Less muscle mass - relatively higher fat content.

Increased VD of fat soluble drugs (increased accumulation).
Decreased VD of water soluble drugs.

Question 10

VO2 max (best measure of aerobic capacity / CV fitness) declines with age, mainly due to…?

Answer 10

Decline in maximum HR

approx. = 220-age in years

Question 11

Ageing muscle shows which characteristic change?

Why does this contribute to falls?

Answer 11

Type 2 fibre atrophy.

These are fast-twitch muscle fibres that allow rapid response.

“Explosive” power shows greater decline - therefore less able to respond rapidly - increased risk of falls. (“explosive muscle power”/type 2 is the thing that is engaged in falls)

Resistance training can improve strength even in 90+ age group.

Question 12

Changes in distribution of fat with ageing:

Answer 12

1. Subcut: decreases
2. Appendicular: decreases
3. Visceral: increases
4. Truncal: increases

Question 13

Is there an increased risk of falls with TCAs as opposed to SSRIs in the elderly?

Answer 13

No

Question 14

Hepatic drug clearance is reduced in old age, mainly due to:

Answer 14

Diminished hepatic blood flow.

Question 15

what is the outcome of elevated p53 in cell lines?

Answer 15

p53 is a signalling marker for cell-growth arrest and apoptosis

Question 16

is grey or white matter more commonly lost in the ageing brain?

Answer 16

typically we see loss of white more than grey. these are the processing neurones

Question 17

What are the two types of reactions in the liver, and what type decreases with age?

Why?

Answer 17

type 1 is oxidative - this type is reduced with ageing. Postulated to be related to change in O2 diffusion due to changes in hepatic blood flow

type 2 is conjugation (glucironidation for eg) remains largely the same.

however there is a huge reserve, so they actually dont have much of a change in synthetic function

Question 18

what happens to the pharmacokinetics in elderly? (volume of distribution)

Answer 18

fat volume goes up (there is also a change of the distribution pattern)

water volume goes down.

there is also a change in the bioavailability of some drugs due to decrease in the small bowel extraction

Question 19

what is the classical symptom associated with spinal canal stenosis?

Answer 19

lower extremity numbness with prolonged weight bearing

Question 20

what is the strongest RF for stroke?

what is the strongest MODIFIABLE RF for stroke?

Answer 20

age

modifiable is HTN

Question 21

what is the hormone that declines most commonly in the ageing population?

cortisol
ACTH
thyrotropin
DHEA
insulin

Answer 21

DHEA